Eknoyan (N Engl J Med 1984;311:915-7) estimated that intradialytic skeletal muscle cramps affect over one-third of hemodialysis patients. These cramps can be extremely painful and are a major cause of patient non-adherence to prescribed hemodialysis therapy. Over a 12-month period, Rocco and Burkart (J Am Soc Nephrol 1993;4:1178-83) reviewed 31,212 hemodialysis sessions in an average of 231 patients and found that missed treatments averaged 1.2±0.2% per month and early termination of dialysis sessions averaged 6.8±0.9% per month. Intradialytic skeletal muscle cramps were the most common single cause of this latter problem, being cited as the reason in 17.9% of the early terminations.
There have been few studies of the pathophysiology of intradialytic skeletal muscle cramps. However, there is general agreement that plasma volume contraction is the initiating event (FIG. 1). This is supported by the fact that typical treatment regimens for these cramps include administration of normal or hypertonic saline, hypertonic glucose and/or hypertonic mannitol, in addition to reducing ultrafiltration rate. However, postdialysis retention of sodium and mannitol may lead to increased thirst, interdialytic weight gain, and elevated blood pressure. Therefore, a number of prophylactic therapies have been advocated, including quinine, nifedipine, creatine, and shakuyaku-kanzo-to. Despite reports of the therapeutic success of these agents, no convincing pharmacologic rationale has been provided to support their claimed efficacy, and quinine, in particular, has an inadequate benefit-to-risk ratio to warrant its therapeutic use except in some patients with malaria. Consequently, there are no currently approved drugs or methods of treatment for cramping during dialysis. Therefore, there is a need for treatments that can prevent or ameliorate skeletal muscle cramps that occur during dialysis.